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Murine Mesenchymal Stromal Cells Retain Biased Differentiation Plasticity Towards Their Tissue of Origin

1
School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
2
Shenzhen Institute of Research and Innovation, The University of Hong Kong, Hong Kong SAR, China
*
Author to whom correspondence should be addressed.
Cells 2020, 9(3), 756; https://doi.org/10.3390/cells9030756 (registering DOI)
Received: 29 February 2020 / Revised: 15 March 2020 / Accepted: 18 March 2020 / Published: 19 March 2020
(This article belongs to the Special Issue Adipose-Derived Stromal/Stem Cells)
Mesenchymal stromal/stem cells (MSCs) reside in many human tissues and comprise a heterogeneous population of cells with self-renewal and multi-lineage differentiation potential, making them useful in regenerative medicine. It remains inconclusive whether MSCs isolated from different tissue sources exhibit variations in biological features. In this study, we derived MSCs from adipose tissue (AT-MSC) and compact bone (CB-MSC). We found that early passage of MSCs was readily expandable ex vivo, whereas the prolonged culture of MSCs showed alteration of cell morphology to fibroblastoid and reduced proliferation. CB-MSCs and AT-MSCs at passage 3 were CD29+, CD44+, CD105+, CD106+, and Sca-1+; however, passage 7 MSCs showed a reduction of MSC markers, indicating loss of stem cell population after prolonged culturing. Strikingly, CB-MSC was found more efficient at undergoing osteogenic differentiation, while AT-MSC was more efficient to differentiate into adipocytes. The biased differentiation pattern of MSCs from adipogenic or osteogenic tissue source was accompanied by preferential expression of the corresponding lineage marker genes. Interestingly, CB-MSCs treated with DNA demethylation agent 5-azacytidine showed enhanced osteogenic and adipogenic differentiation, whereas the treated AT-MSCs are less competent to differentiate. Our results suggest that the epigenetic state of MSCs is associated with the biased differentiation plasticity towards its tissue of origin, proposing a mechanism related to the retention of epigenetic memory. These findings facilitate the selection of optimal tissue sources of MSCs and the ex vivo expansion period for therapeutic applications. View Full-Text
Keywords: mesenchymal stromal cell; differentiation; tissue of origin; prolonged culture; epigenetic memory mesenchymal stromal cell; differentiation; tissue of origin; prolonged culture; epigenetic memory
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Ng, T.T.; Mak, K. .-M.; Popp, C.; Ng, R.K. Murine Mesenchymal Stromal Cells Retain Biased Differentiation Plasticity Towards Their Tissue of Origin. Cells 2020, 9, 756.

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